Sacituzumab Tirumotecan as Second-Line Treatment for Penile Cancer (PERSEUS)

September 9, 2026 updated by: Latin American Cooperative Oncology Group

A Single-arm Phase II Trial of Sacituzumab Tirumotecan (Sac-TMT; MK-2870) as Second-line Treatment for Advanced/Metastatic Penile Squamous Cell Carcinoma: PERSEUS TRIAL (LACOG 1924)

This is a single-arm, Phase 2 clinical trial (PERSEUS TRIAL / LACOG 1924) evaluating the efficacy, safety, and tolerability of sacituzumab tirumotecan (sac-TMT; MK-2870) as a second-line treatment for patients with advanced or metastatic penile cancer. Penile squamous cell carcinoma (PSCC) is a rare and aggressive cancer with limited treatment options once disease progression occurs after initial platinum-based chemotherapy. Sacituzumab tirumotecan is an antibody-drug conjugate (ADC) designed to target TROP-2, a protein frequently expressed at high levels on penile cancer cells. By binding to TROP-2, sac-TMT delivers a anti-cancer payload directly to the tumor cells. All participants in this trial will receive sacituzumab tirumotecan administered via intravenous (IV) infusion every 2 weeks. The main goal of this study is to determine the percentage of patients whose tumors shrink or disappear after receiving sacituzumab tirumotecan (Objective Response Rate).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Penile squamous cell carcinoma (PSCC) represents a significant unmet medical need, particularly in low- and middle-income regions where the incidence is higher. For patients with disease recurrence or metastasis following first-line platinum-based chemotherapy, standard second-line therapeutic options offer poor response rates and a dismal median overall survival of 4 to 5 months. Recent findings show that over 80% of PSCC cases express high levels of TROP-2, making it a key therapeutic target. Sacituzumab tirumotecan (sac-TMT; MK-2870) is a novel antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 monoclonal antibody linked to a topoisomerase I inhibitor payload (KL610023). Study Design & Intervention: This is an open-label, multicenter, single-arm Phase 2 trial enrolling 37 adult patients with advanced/metastatic PSCC who experienced disease progression on or after first-line platinum-based chemotherapy. Participants receive sacituzumab tirumotecan at a dose of 4 mg/kg via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle for up to 8 cycles, or until disease progression, unacceptable toxicity, or consent withdrawal.

Primary Endpoint: Objective Response Rate (ORR), defined as the proportion of participants achieving a confirmed Complete Response (CR) or Partial Response (PR) assessed by the investigator using RECIST v1.1 criteria. Secondary Endpoints:Independent Central Review Objective Response Rate (ORR-ICR) Disease Control Rate (DCR) and Clinical Benefit Rate (CBR at 24 weeks) Duration of Response (DoR) Progression-Free Survival (PFS) and Overall Survival (OS) Safety and toxicity profile (evaluated via CTCAE v5.0) Treatment compliance and post-progression therapies Exploratory Research: Assessment of baseline tumor TROP-2 expression, HPV16 status, ctDNA dynamics, and molecular mechanisms of acquired resistance. Statistical Design: The trial utilizes Simon's two-stage Minimax design (18 participants accrued in Stage 1, expanding to 33 total evaluable participants if $\ge5$ responses are observed). Accounting for a 10% drop-out rate, a total of 37 participants will be enrolled.

Study Type

Interventional

Enrollment (Estimated)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
    • Ceará
      • Fortaleza, Ceará, Brazil, 60135-237
        • Instituto D'Or de Pesquisa e Ensino Ceará
        • Principal Investigator:
          • Karine Martins da Trindade
        • Contact:
      • Fortaleza, Ceará, Brazil, 60430-230
        • ICC - Instituto do Câncer do Ceará
        • Principal Investigator:
          • João Paulo Holanda Soares
        • Contact:
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 40050-410
        • Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel (Oncoclínicas)
        • Contact:
        • Principal Investigator:
          • Carolina Alves Costa Silva
    • Federal District
      • Brasília, Federal District, Brazil, 70200-730
        • Hospital Sírio-Libanês DF
        • Principal Investigator:
          • Fernando Sabino Marques Monteiro
        • Contact:
    • Pará
      • Belém, Pará, Brazil, 66093-020
        • IEPAM - Instituto de Ensino e Pesquisa da Amazônia
        • Principal Investigator:
          • Manuel Caitano Dias Ferreira Maia
        • Contact:
    • Pernambuco
      • Recife, Pernambuco, Brazil, 52011-000
        • ISEP - Instituto Santa Joana de Ensino e Pesquisa (Rede Américas)
        • Contact:
        • Principal Investigator:
          • Andréa Lopes Ponte de Andréa Lopes Ponte de
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062-000
        • Liga Norte Riograndense Contra o Cancer
        • Contact:
        • Principal Investigator:
          • Andrea Juliana Pereira de Santana Gomes
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, Rio Grande do Sul
        • Futtura Oncologia - Hub de Pesquisa Clínica
        • Principal Investigator:
          • Luísa Rabeno Fasolo
        • Contact:
      • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
        • ISCMPA - Santa Casa de Porto Alegre
        • Principal Investigator:
          • André Poisl Fay
        • Contact:
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Hospital de Amor de Barretos
        • Contact:
        • Principal Investigator:
          • Daniel D'Almeida Preto
      • São Paulo, São Paulo, Brazil, 01323-030
        • BP - A Beneficência Portuguesa de São Paulo
        • Contact:
        • Principal Investigator:
          • Rodrigo Coutinho Mariano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically- or cytologically confirmed diagnosis of penile squamous cell carcinoma.
  • Metastatic or locally advanced disease not amenable to curative intent-therapy (e.g., surgery, radiotherapy, chemoradiotherapy) in the opinion of the investigator.
  • Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology (lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions).
  • Disease progression on first-line platinum-based chemotherapy for locally advanced/metastatic disease or disease progression within 12 months of (neo) adjuvant chemotherapy completion.
  • Male participant at least 18 years of age at the time of providing informed consent.
  • Male Participants (Reproductive Potential): If capable of producing sperm, agrees to refrain from donating sperm and use a penile/external condom when having intercourse with a partner of childbearing potential, plus partner use of an additional contraceptive method, during the intervention period and for at least 120 days after the last dose of study intervention.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
  • Life expectancy of at least 12 weeks.
  • Provide an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion from any site not previously irradiated; formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides (recommended 22-28 slides).
  • Recovery from AEs due to previous anticancer therapies to Grade <=1 or baseline (except for alopecia and vitiligo); participants with endocrine-related AEs adequately treated with hormone replacement therapy are eligible.
  • Adequate organ function defined by the laboratory values (specimens collected within 14 days before the start of study intervention):
  • Absolute Neutrophil Count (ANC) >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L
  • Measured or calculated Creatinine Clearance > 30 mL/min
  • Total Bilirubin <= 1.5 x ULN OR direct bilirubin < ULN for participants with total bilirubin levels > 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) <= 2.5 x ULN (<= 5 x ULN for participants with liver metastases)
  • Serum Albumin >= 3.0 g/dL
  • INR or PT < 1.5 x ULN; aPTT < 1.5 x ULN (unless receiving anticoagulant therapy within therapeutic range)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Willing and able to comply with study procedures, laboratory tests, and other requirements of the study.
  • HIV-infected participants are eligible if well-controlled on ART (CD4+ T-cell count >350 cells/mm3, confirmed HIV RNA <50 copies/mL for at least 12 weeks, no AIDS-defining opportunistic infections within past 12 months, and on a stable regimen for at least 4 weeks without strong CYP3A4 inducers/inhibitors).
  • Participants with chronic Hepatitis B virus (HBsAg positive) are eligible if received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before enrollment.
  • Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening and completed curative antiviral therapy at least 4 weeks before enrollment.

Exclusion Criteria:

  • History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
  • Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
  • Uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months before first dose (NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, or QTcF >480 ms).
  • Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC).
  • Received prior treatment with a topoisomerase 1 inhibitor-containing ADC.
  • Received prior systemic anticancer therapy within 2 weeks before first dose of study intervention.
  • Received prior radiotherapy within 2 weeks before first dose, has radiation-related toxicities requiring corticosteroids, and/or has had radiation pneumonitis (palliative radiotherapy <= 2 weeks for non-CNS disease completed at least 7 days before first dose is permitted).
  • Received a live or live-attenuated vaccine within 30 days before first dose of study intervention.
  • Currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued (washout period required is 2 weeks).
  • Currently enrolled on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy.
  • Received an investigational agent or used an investigational device within 4 weeks before first dose of study intervention.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years (except adequately treated basal/squamous cell skin cancer, carcinoma in situ, or low-risk early-stage prostate cancer).
  • History of CNS metastases and/or carcinomatous meningitis.
  • Active infection requiring systemic therapy within 4 weeks prior to first dose of study treatment (except permitted treated HIV, HBV, HCV).
  • Severe hypersensitivity (Grade >=3) to study intervention, any of its excipients, and/or to another biologic therapy.
  • Major surgery or significant traumatic injury within 4 weeks before first dose, or anticipation of need for major surgery during treatment.
  • History of (noninfectious) pneumonitis/interstitial lung disease requiring steroids or current pneumonitis/interstitial lung disease.
  • Any condition, therapy, laboratory abnormality, or circumstances that might confound study results or interfere with compliance in the opinion of the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sacituzumab Tirumotecan
Participants receive sacituzumab tirumotecan (sac-TMT; MK-2870) at a dose of 4 mg/kg via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle for up to 8 cycles, or until disease progression, unacceptable toxicity, or consent withdrawal, whichever comes first.
Drug: Sacituzumab Tirumotecan
Sacituzumab tirumotecan is an ADC consisting of 3 major components: 1) a humanized antihuman TROP2 mAb of IgG1 class; 2) an ADC-coupling linker with a methyl sulfonyl moiety as the leaving group; and 3) a cytotoxic drug in the class of topoisomerase 1 inhibitors, KL610023. The drug-antibody ratio of sacTMT is 7.4. Sacituzumab tirumotecan is designed to enhance the binding between the antibody and linker, which can prolong the half-life of ADC molecules in serum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) by Investigator Assessment
Time Frame: Up to 8 cycles (each cycle is 28 days)
Percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Up to 8 cycles (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate by Independent Central Review (ORR-ICR)
Time Frame: Up to 8 cycles (each cycle is 28 days)
Percentage of participants who achieve a confirmed CR or PR as assessed by Independent Central Review using RECIST v1.1.
Up to 8 cycles (each cycle is 28 days)
Disease Control Rate (DCR)
Time Frame: Up to 8 cycles (each cycle is 28 days)
Percentage of participants who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as assessed by the investigator using RECIST v1.1
Up to 8 cycles (each cycle is 28 days)
Clinical Benefit Rate (CBR)
Time Frame: At 24 weeks
Percentage of participants who achieve CR, PR, or SD lasting for at least 24 weeks from enrollment, as assessed by the investigator using RECIST v1.1.
At 24 weeks
Duration of Response (DoR)
Time Frame: Up to 36 months
Time from the first documented evidence of confirmed response (CR or PR) until disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
Up to 36 months
Progression-Free Survival (PFS)
Time Frame: Up to 36 months
Time from the date of enrollment until the first documented disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
Up to 36 months
Overall Survival (OS)
Time Frame: Up to 36 months
Time from the date of enrollment to the date of death due to any cause.
Up to 36 months
Incidence and Severity of Adverse Events (Safety and Toxicity)
Time Frame: From baseline up to 30 days after the last dose of study intervention.
Rate of overall treatment-emergent adverse events (TEAEs) and Grade 3 or higher adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
From baseline up to 30 days after the last dose of study intervention.
Treatment Compliance
Time Frame: Up to 8 cycles (each cycle is 28 days)
Number and percentage of participants whose treatment was reduced, delayed, or permanently discontinued, categorized by reason (e.g., tumor progression, adverse events, or withdrawal of consent).
Up to 8 cycles (each cycle is 28 days)
Post-Progression Therapies
Time Frame: Up to 36 months
Descriptive summary of subsequent anti-cancer therapies administered after disease progression on sacituzumab tirumotecan.
Up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Latin American Cooperative Oncology Group

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Fernando Cotait Maluf, Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein
  • Principal Investigator: Karine Martins da Trindade, Instituto D'or de Pesquisa e Ensino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2027

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

September 2, 2026

First Submitted That Met QC Criteria

September 9, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 9, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • LACOG 1924

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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